Chromosomes carry the genetic information necessary for an organism’s development and function. Human cells typically contain 23 pairs, totaling 46 chromosomes. An incorrect number of chromosomes in a cell is known as aneuploidy. This article explains how such errors occur during cell division.
The Blueprint: Chromosomes and Cell Division Basics
Cells divide for various reasons, including growth, repair of damaged tissues, and reproduction. During this process, the genetic material, organized into chromosomes, must be accurately duplicated and then distributed equally to the new “daughter” cells. This precise distribution ensures that each new cell receives a complete and correct set of genetic instructions.
There are two main types of cell division: mitosis and meiosis. Mitosis occurs in somatic, or body, cells and produces two genetically identical daughter cells, each with a full set of chromosomes. Meiosis, on the other hand, is a specialized division that occurs in germ cells to produce reproductive cells (sperm and egg), resulting in four unique daughter cells, each with half the number of chromosomes. The intricate nature of these processes means errors can occur if chromosome movement is disrupted.
Primary Mechanism of Error: Nondisjunction
Nondisjunction, the failure of chromosomes to separate properly during cell division, is the most frequent cause of an incorrect chromosome number. This error can occur in either meiosis, affecting reproductive cells, or in mitosis, affecting body cells.
Nondisjunction in meiosis leads to gametes (sperm or egg cells) with an abnormal number of chromosomes. If such a gamete is involved in fertilization, the resulting embryo will have an incorrect chromosome count in every cell of its body. This can happen in two ways:
Nondisjunction in Meiosis I
Homologous chromosomes (the pairs inherited from each parent) fail to separate, with both moving to the same pole. The resulting gametes will either have an extra chromosome or be missing one.
Nondisjunction in Meiosis II
Sister chromatids (the duplicated halves of a single chromosome) fail to separate. Two of the four resulting gametes will have a normal chromosome number, while the other two will be aneuploid (one with an extra chromosome, one missing a chromosome). Meiosis I nondisjunction is considered a more common cause of aneuploidy than Meiosis II nondisjunction.
Nondisjunction can also occur during mitosis, the division of body cells after conception. This results in mosaicism, where a developing individual has a mixture of cells: some with the correct number of chromosomes and some with an incorrect number. The abnormality is present in only a subset of cells. This leads to varying effects depending on which tissues are affected and to what extent.
Other Ways Chromosomes Go Astray
While nondisjunction is the primary mechanism, other distinct processes can also lead to an incorrect number of chromosomes.
Anaphase Lag
This occurs when a chromosome or chromatid fails to properly migrate to one of the daughter nuclei during cell division. Instead, it lags behind and may not be incorporated into either new nucleus, leading to its loss. Anaphase lag results in one daughter cell receiving a complete set of chromosomes, while the other ends up missing one. This mechanism is a significant contributor to chromosomal mosaicism, particularly observed in early embryonic development.
Endoreduplication
This involves a cell duplicating its entire set of chromosomes without undergoing cell division. This results in cells having multiple complete sets of chromosomes, such as four sets instead of the usual two. This is distinct from aneuploidy, which involves the gain or loss of individual chromosomes rather than entire sets.
Factors Influencing Errors
Several factors can influence the likelihood of these chromosomal errors occurring. Advanced maternal age is a well-established and significant factor contributing to an increased risk of nondisjunction in eggs. As women age, the cellular mechanisms responsible for proper chromosome segregation in their eggs may become less efficient. This decline can increase the chance of errors during meiosis.
While less definitively understood, certain environmental exposures or lifestyle factors might also play a minor role in increasing the risk of chromosomal errors. However, the evidence for these environmental influences is not as robust or widespread as that for maternal age. The intricate processes of cell division are susceptible to various influences.